GIP (gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide) is a gastrointestinal hormone belonging to the glucagon/secretin family. GIP is called incretin, as with GLP-1 (glucagon-like peptide 1), and is secreted by K cells present in the small intestine upon intake of lipids or carbohydrates.
GIP is known to promote insulin secretion from pancreatic β cells and to enhance the uptake of glucose into fat cells in the presence of insulin. Therefore, the action of GIP is considered to be partly responsible for obesity. It has been reported that obesity is actually suppressed by inhibiting the functions of GIP (Non Patent Literature 1).
It has been further reported that GIP is partly responsible for insulin resistance (Non Patent Literature 1). When insulin resistance occurs, glucose-absorbing effects mediated by insulin are reduced, consequently causing hyperinsulinemia. It is recognized that hyperinsulinemia is a primary cause leading to the occurrence of various lifestyle-related diseases including obesity. The prevention or amelioration of insulin resistance is also important in terms of the risk reduction of the lifestyle-related diseases.
GIP is also known to have inhibitory effect of gastric secretion or gastric motility (Patent Literatures 1 to 3). The suppression of elevation of GIP is presumably effective for the enhancement of digestibility after eating or the amelioration of heavy feeling in the stomach.
Thus, the measurement of the concentration of GIP in blood is important for the evaluation of such diseases or therapeutic drugs therefor.
GIP is known to include an active form having physiological activity and a nonactive form lacking physiological activity. Specifically, in humans, prepro-GIP is processed into active GIP (also referred to as “GIP(1-42)”) in K cells distributed in the stomach, the duodenum, and the upper small intestine. Then, N-terminal 2 amino acids of the active GIP are cleaved off by DPP-4 to form nonactive GIP (also referred to as “GIP(3-42)”). Thus, in the quantification of in vivo GIP, the mere measurement of the total amount of the active and nonactive forms does not permit accurate determination of the effects of therapeutic drugs, the risk of lifestyle-related diseases, etc.
An active GIP quantification kit (Immuno-Biological Laboratories Co, Ltd. (IBL)) is commercially available as a conventional approach for measuring active GIP. The problems of this kit are that 1) active GIP concentrations in blood after eating are higher than the quantification limit of the kit, 2) the coefficient of variation exceeds 10% for different dilution ratios, and 3) a higher dilution ratio leads to a higher measurement level. Recently, it has been reported that active GIP having a concentration of 5 to 4,000 pg/mL can be quantified by ELISA using an anti-active GIP monoclonal antibody prepared by using, as an immunogen, a peptide consisting of N-terminal 6 amino acid residues of GIP(1-42) (Non Patent Literature 2). It has also been reported that active GIP having a concentration of 7 to 500 pg/mL can be quantified by ELISA using an anti-active GIP monoclonal antibody prepared by using, as an immunogen, a peptide consisting of N-terminal 7 amino acid residues of GIP(1-42) (Patent Literature 4).    (Patent Literature 1) WO 01/87341    (Patent Literature 2) JP2006-213598A    (Patent Literature 3) JP5-95767A    (Patent Literature 4) JP2013-138638A    (Non Patent Literature 1) Miyawaki K et al., Nat Med. 8 (7): 738-42, 2002    (Non Patent Literature 2) Jason S. Troutt et al., Clinical Chemistry, 57 (6): 849-855 (2011)